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| Credit WHO |
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Over the past 10 years we've seen a number of promising drugs used to treat Ebola cases under the framework of compassionate use/expanded access, but without proper testing, the merits - or downsides - of these treatments remain impossible to quantify.
Some early treatments have proved less than stellar (see Clinical Trial Of Ebola Drug TKM-Ebola Halted, No Therapeutic Benefit and NEJM: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea), but the jury remains out on several others.The challenge is finding an ethical way to blind-test several treatment options in what is already a chaotic, and often less-than-modern, field environment. Further complicating matters, there's more than one kind of Ebolavirus - meaning that the results from one epidemic may not carry over to another.
Six weeks ago, the World Health Organization announced the creation of a WHO R&D Blueprint – Ad-hoc Expert Consultation on clinical trials for Ebola Therapeutics, described as:
Deliberations on design options for randomized controlled clinical trials to assess the safety and efficacy of investigational therapeutics for the treatment of patients with Ebola virus diseaseThe report goes on to warn:
Given the size of Ebola outbreaks it is anticipated that one single epidemic may not generate conclusive evidence and therefore it is important to plan for and implement a protocol that would allow the scientific community to collect and accumulate robust evidence over a number of outbreaks over a period of time and to move away from seeing each outbreak as a discrete episode.
Also important is the need to consider the potential operational challenges with the implementation of various trial designs and, with the administration and monitoring of different investigational therapeutic agents. The anticipation of such potential challenges is critical, so appropriate mitigation measures are implemented in advance, if pertinent.
Currently, the therapeutics under consideration include Zmapp, GS-5734, REGN monoclonal antibody combination, Favipiravir, and mAb114. All have pros and cons, and no clear winner has emerged.
Despite the considerable challenges that lie ahead, today the World Health Organization has announced that the first-ever multi-drug Ebola trials will begin in the current outbreak in the DRC.
Democratic Republic of the Congo begins first-ever multi-drug Ebola trial
26 November 2018
News Release
The Ministry of Health of the Democratic Republic of the Congo (DRC) today announced that a randomized control trial has begun to evaluate the effectiveness and safety of drugs used in the treatment of Ebola patients. The trial is the first-ever multi drug trial for an Ebola treatment. It will form part of a multi-outbreak, multi-country study that was agreed to by partners under a World Health Organization (WHO) initiative.
“While our focus remains on bringing this outbreak to an end, the launch of the randomized control trial in DRC is an important step towards finally finding an Ebola treatment that will save lives,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Until now, patients have been treated under a compassionate use protocol, with drugs that showed promise and had a good safety profile in laboratory conditions. The giant step DRC is taking now will bring clarity about what works best, and save many lives in years to come. We hope to one day say that the death and suffering from Ebola is behind us.”
Until now, over 160 patients have been treated with investigational therapeutics under an ethical framework developed by WHO, in consultation with experts in the field and the DRC, called the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI). The MEURI protocol was not designed to evaluate the drugs. Now that protocols for trials are in place, patients will be offered treatments under that framework in the facilities where the trial has started. In others, compassionate use will continue up to the time when they join the randomization. Patients will not be treated noticeably differently from before, though the treatment they receive will be decided by random allocation. The data gathered will become standardized and will be useful for drawing conclusions about the safety and efficacy of the drugs.
“Our country is struck with Ebola outbreaks too often, which also means we have unique expertise in combatting it,” said Dr Olly Ilunga, Minister of Health of the DRC. “These trials will contribute to building that knowledge, while we continue to respond on every front to bring the current outbreak to an end.”
In October, WHO convened a meeting of international organizations, United Nations partners, countries at risk of Ebola, drug manufacturers and others to agree on a framework to continue trials in the next Ebola outbreak, whenever and wherever that is. Over time, this will lead to an accumulation of evidence that will help to draw robust conclusions across outbreaks about the currently available drugs, and any new ones that may come along.
At the heart of the long term plan and the current trial is always the goal to ensure that patients with Ebola and their communities are treated with respect and fairness. All patients should be provided with the highest level of care and have access to the most promising medications.
The current trial is coordinated by WHO, and led and sponsored by the DRC’s National Institute for Biomedical Research (INRB), in partnership with the DRC Ministry of Health, the National Institute of Allergy and Infectious Diseases (NIAID) which is part of the United States’ National Institutes of Health, The Alliance for International Medical Action (ALIMA) and other organizations.
The deliberations of the consultation are available here.
